title: Blockade of the formation of insoluble ubiquitinated protein aggregates by EGCG3"Me in the alloxan-induced diabetic kidney.
abstract: BACKGROUND
  Renal accumulation of reactive carbonyl compounds (RCCs) has been linked to the progression of diabetic nephropathy. We previously demonstrated that carbonyl stress induces the formation of amino-carbonyl cross-links and sharply increases the content of β-sheet-rich structures, which is the seed of insoluble aggregates formation, and tea catechin (-)-epigallocatechin 3-gallate (EGCG) can reverse this process in vitro and in vivo. In this study, methylated derivative (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3"Me) was hypothesized to neutralize carbonyl stress mediating the formation of insoluble ubiquitinated protein (IUP) aggregates, and reduce the early development of diabetic nephropathy.
  
  
  RESULTS
  Diabetes was induced in mice by intraperitoneally injecting alloxan monohydrate (200 mg/kg/d) twice and administering EGCG3"Me by gavage for 15 d. Reagent case and western blot results showed that, in diabetic kidneys, the carbonyl proteins in the serum increased; and in insoluble protein fraction, 4-hydroxynonenal-modified proteins, IUP aggregates and p62 accumulated; FT-IR study demonstrated that the lipid content, anti-parallel β-sheet structure and aggregates increased. EGCG3"Me treatment could effectively reverse this process, even better than the negative control treatment.
  
  
  CONCLUSIONS
  EGCG3"Me exhibiting anti-β-sheet-rich IUP aggregate properties, maybe represents a new strategy to impede the progression of diabetic nephropathy and other diabetic complications.
authors.affiliation: Key Laboratory of Ministry of Education for Tea Science, Hunan Agricultural University, Changsha, Hunan Province, China ; Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Cai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhong
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Li
authors.forename: Jianan
authors.initials: J
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Guoan
authors.initials: G
authors.lastname: Luo
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D050050:Protein Carbonylation / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared; D057149:Ubiquitinated Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D001786:Blood Glucose; D057149:Ubiquitinated Proteins; D005707:Gallic Acid; C573278:epigallocatechin-3-O-(3''-O-methyl)-gallate